L-fucose, also referred to as 6-deoxy-L-galactose, is a monosaccharide that is a component of some N- and O-linked glycans and glycolipids in animals. (See Becker and Lowe, Glycobiology 13:41R-51R (2003).) Fucose is typically added as a terminal modification to glycans, including glycans attached to blood group antigens, selectins and antibodies. Fucose can be attached to glycans via α(1,2)-, α(1,3)-, α(1,4)- and α(1,6)-linkages by specific fucosyltransferases. α(1,2)-fucose linkages are typically associated with the H-blood group antigens. α(1,3)- and α(1,4)-fucose linkages are associated with modification of LewisX antigens. α(1,6)-fucose linkages are associated with N-linked GlcNAc molecules, such as those on antibodies.
Fucosylation of proteins is believed to play a role in mammalian development. Mice homozygous for a targeted mutation of the FX gene exhibit pleiotropic abnormalities including a lethal phenotype. Reduced recovery of mice from heterozygous crosses was also reported. (Becker et al., Mammalian Genome 14:130-139 (2003). Aberrant protein fucosylation has been proposed to be associated with human disease, including up-regulation of sialyl LewisX and sialyl Lewisy in cancers. These glycans are ligands for E- and P-selectin molecules. In it speculated that increases in sialyl LewisX and sialyl Lewisy glycans on cancer cells increases metastases through interaction with E- and P-selectins on endothelium. Increased fucosylated glycans have also been observed in patients with rheumatoid arthritis. Currently, however, there are no approved therapeutic approaches targeting protein fucosylation levels.